1. Field of the Invention
This invention relates to the synthesis of a polycaprolactone fumarate polymer useful as a material for a biocompatible scaffold for tissue engineering.
2. Description of the Related Art
Polycaprolactone fumarate (PCLF) is a cross-linkable derivative of polycaprolactone (PCL) that has been shown to be promising material for tissue engineering applications involving both the repair of segmental nerve defects as well as a bone substitute. PCLF has previously been synthesized by condensation polymerization of fumaryl chloride with a polycaprolactone ether diol of molecular weights 530, 1200, or 2000 g mol−1. Previous work has shown that PCLF synthesized from PCL ether diol with an Mn of 2000 g mol−1 results in PCLF with an Mn of 7,000 to 18,000 g mol−1, and has the most favorable material properties over other PCLF formulations synthesized from PCL 530 or 1250. Therefore PCLF synthesized from PCL2000 has been used for the production of nerve conduits to repair segmental nerve defects. These PCLF nerve conduits have been shown to support robust nerve regeneration across the one centimeter rat sciatic nerve defect model and have warranted future clinical studies.
In preparation for upcoming clinical trials, the potential degradation products released from polycaprolactone fumarate scaffolds were analyzed. During the course of this degradation study, it was determined that diethylene glycol (also known as 2-hydroxyethyl ether) (DEG) can be released during hydrolysis as one degradation product from the previously studied polycaprolactone fumarate. The release of diethylene glycol is of concern because it is has been reported to be a toxin and makes up roughly 5 percent of a polycaprolactone fumarate composition formed from polycaprolactone ether diol, an amount that currently exceeds United States Food and Drug Administration limits.
What is needed therefore is a biocompatible polycaprolactone fumarate formulation that releases no diethylene glycol or other undesirable byproducts during degradation.